The structure for GNAS is solved for the canonical P63092-1 isoform only, and little is known about what the special region of XLas or ALEX looks like. NESP55 is a protein product completely unrelated to the GNAS protein. It undergoes extensive posttranslation processing, and is sometimes grouped as a granin. Nearly nothing is known about its structure; protein structure prediction predicts a mostly disordered protein with an N-terminal globular domain made up of alpha-helices. Clinical significance Mutations in GNAS products are associated with: Albright hereditary osteodystrophy pseudohypoparathyroidism type Ia and Ib pseudopseudohypoparathyroidism McCune–Albright syndrome Myxoma Mutations in this gene also result in progressive osseous heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors. Mutations in the repeat region of the XL exon leads to a hyperactive form of XLas due to lowered interaction with ALEX. As XLas is expressed in platelets, the risk of bleeding is elevated. Many alleles in mice have been constructed for analyzing disease associations. Mice with this gene half knocked-out and half-mutated (tm1Jop/Oedsml) display increased heart weight, increased startle reflex, and abnormalities in bone structure and mineralization; some other alternations can be lethal. Metabolic problems resembling pseudohypoparathyroidism are seen in heterozygous mutated (wt/Oedsml) mice. Knocking out the antisense transcript is known to, at minimum, cause methylation defects. Interactions G protein-coupled receptor-activated Gsα binds to the enzyme adenylyl cyclase, increasing its rate of conversion of ATP to cyclic AMP. Gsα has been shown to interact with RIC8A. References Further reading External links WikiGene index for literature mentioning this gene: GNAS: human, mouse, rat Nespas: human, mouse Human proteins